Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung. |
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| Authors: | Julien D F Licchesi William H Westra Craig M Hooker James G Herman |
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| Affiliation: | Cancer Biology Program at the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA. |
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| Abstract: | PURPOSE: According to current models of tumorigenesis, the progression of phenotypic changes culminating in overtly malignant carcinoma is driven by genetic and epigenetic alterations. The recognition of an early form of glandular neoplasia termed atypical adenomatous hyperplasia (AAH), a precursor lesion from which lung adenocarcinomas arise, provides an opportunity for characterizing early epigenetic alterations involved in lung tumorigenesis. EXPERIMENTAL DESIGN: We evaluated AAHs, adjacent normal lung tissue, and synchronous lung adenocarcinomas for promoter hypermethylation of genes implicated in lung tumorigenesis (p16, TIMP3, DAPK, MGMT, RARbeta, RASSF1A, and hTERT). RESULTS: For individual genes and the number of genes methylated, we observed a significant increase in the frequency of promoter hypermethylation in the histologic progression from normal to AAH, with low-grade or high-grade atypia, and finally to adenocarcinoma (P(trend)
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